TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur concomitantly with KRAS mutations in the mucinous type

Markus Rechsteiner, Anne-Katrin Zimmermann, Peter J Wild, Rosmarie Caduff, Adriana von Teichman, Daniel Fink, Holger Moch, Aurelia Noske
Experimental and Molecular Pathology 2013, 95 (2): 235-41

AIMS: Epithelial ovarian cancer (EOC) can be classified into four major types (serous, endometrioid, clear cell, mucinous). The prevalence of driver gene mutations in the different subtypes is controversial. High-grade serous carcinomas show frequent TP53 mutations, whereas KRAS and BRAF mutations are less common. In non-serous EOC, the relevance of these gene mutations remains to be elucidated.

METHODS: We investigated 142 formalin-fixed, paraffin-embedded EOC, including serous (n=63), endometrioid (n=29), clear cell (n=25), mucinous (n=14), and others (n=11) for mutations in TP53 exons 5-8, KRAS exons 2 and 3, and BRAF exon 15 by pyro-sequencing using the GS Junior 454 platform. The mutational status was correlated with clinicopathological features and patient overall survival.

RESULTS: We identified mutations in the coding region of TP53 in 51.4% (73/142), and of KRAS in 9.9% (14/142) but not of BRAF. TP53 mutations occurred frequently not only in high-grade serous carcinomas (58.7%), but also in mucinous (57%) and clear cell EOC (52%). TP53 mutations were associated with high-grade carcinomas (p=0.014), advanced FIGO stage (p=0.001), intraoperative residual disease >1cm (p=0.004), as well as poor overall survival (p=0.002). KRAS mutations were mainly identified in mucinous EOC (57%) and were concomitantly with TP53 mutations in five mucinous carcinomas (36%).

CONCLUSIONS: TP53 gene driver mutations are a common feature of all advanced ovarian cancer subtypes, whereas BRAF mutations seem to be a rare event in EOC. KRAS mutations with synchronous TP53 mutations occur predominantly in low-grade mucinous carcinomas, suggesting a specific molecular background of this ovarian cancer type.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"